Radicals are inevitable intermediates during the charging and discharging of organic redox electrodes. The increase of the reactivity of the radical intermediates is desirable to maximize the capacity and enhance the rate capability but is detrimental to cycling stability. Therefore it is a great challenge to controllably balance the redox reactivity and stability of radical intermediates to optimize the electrochemical properties with a good combination of high specific capacity, excellent rate capability and long-term cycle life. Herein, we reported the redox and tunable stability of radical intermediates in covalent organic frameworks (COFs) considered as high capacity and stable anode for sodium-ion batteries. The comprehensive characterizations combined with theoretical simulation confirmed that the redox of C-O• and α-C radical intermediates play an important role in the sodiation/desodiation process. Specifically, the stacking behavior could be feasibly tuned by the thickness of 2D COFs, essentially determining the redox reactivity and stability of the α-C radical intermediates and their contributive capacity. The modulation of reversible redox chemistry and stabilization mechanism of radical intermediates in COFs offer a novel entry to design novel high performance organic electrode materials for energy storage and conversion.

Predictive and mechanistically driven access to polynuclear oxo clusters and related materials remains a grand challenge of inorganic chemistry. We here introduce a novel strategy for synthetic control over highly sought-after transition metal {MO} cubanes. They attract interest as molecular water oxidation catalysts that combine features of both heterogeneous oxide catalysts and nature's cuboidal {CaMnO} center of photosystem II. For the first time, we demonstrate the outstanding structure-directing effect of straightforward inorganic counteranions in solution on the self-assembly of oxo clusters. We introduce a selective counteranion toolbox for the controlled assembly of di(2-pyridyl) ketone (dpk) with M(OAc) (M = Co, Ni) precursors into different cubane types. Perchlorate anions provide selective access to type 2 cubanes with the characteristic {HO-M(OR)-OH} edge-site, such as [Co(dpy-C{OH}O)(OAc)(HO)](ClO). Type 1 cubanes with separated polar faces [Co(dpy-C{OH}O)(L2)] (L2 = OAc, Cl, or OAc and HO) can be tuned with a wide range of other counteranions. The combination of these counteranion sets with Ni(OAc) as precursor selectively produces type 2 Co/Ni-mixed or {NiO} cubanes. Systematic mechanistic experiments in combination with computational studies provide strong evidence for type 2 cubane formation through reaction of the key dimeric building block [M(dpy-C{OH}O)(HO)] with monomers, such as [Co(dpy-C{OH}O)(OAc)(HO)]. Furthermore, both experiments and DFT calculations support an energetically favorable type 1 cubane formation pathway via direct head-to-head combination of two [Co(dpy-C{OH}O)(OAc)(HO)] dimers. Finally, the visible-light-driven water oxidation activity of type 1 and 2 cubanes with tuned ligand environments was assessed. We pave the way to efficient design concepts in coordination chemistry through ionic control over cluster assembly pathways. Our comprehensive strategy demonstrates how retrosynthetic analyses can be implemented with readily available assembly directing counteranions to provide rapid access to tuned molecular materials.

The preparation and photophysical properties of two heavier main group element analogues of boron-dipyrromethene (BODIPY) chromophores are described. Specifically, we have prepared dipyrrin complexes of dichlorogallate (GADIPY) or phenylphosphenium (PHODIPY) units. Whereas cationic PHODIPY is labile, decomposing to a phosphine over time, GADIPY is readily prepared in good yield as a crystalline solid having moderate air- and water-stability. Crystallographically characterized GADIPY displays intense green photoluminescence (λ = 505 nm, Φ = 0.91 in toluene). These inaugural heavier main group element analogues of BODIPY offer a glimpse into the potential for elaboration to a panoply of chromophores with diverse photophysical properties.

Spiro- and bridged bicyclic structures are in demand for their sp3-rich frameworks that offer unique physiochemical properties and precisely positioned substituent groups. In order to rapidly access such molecules in a cross-coupling fashion we describe olefin-amine (OLA) reagents for the transformation of aldehydes and ketones into all three topological types of bicyclic N-heterocycles: bridged, spiro-, and fused rings. The OLA reagents are easily prepared and allow the synthesis of complex molecular frameworks under operationally simple conditions that tolerate a wide array of functional groups. Investigations into the Mn or Fe promoted reaction pathway support a metal hydride hydrogen atom transfer (MH-HAT) to generate a C-centered radical that undergoes addition to an unactivated imine, leading to an N-centered radical. A catalytic cycle featuring regeneration of the metal catalyst by O2 and a second HAT to form the unprotected saturated N-heterocycle appears to be operative.

The stability of a battery is strongly depended on the feature of solid electrolyte interphase (SEI). The electrical double layer forms prior to the formation of SEI at the interface between Li metal anode and electrolyte. The fundamental understanding on the regulation of the SEI structure and stability on Li surface through structure of electrical double layer is highly necessary for safe batteries. Herein the interfacial chemistry of SEI is correlated with the initial Li surface adsorption electrical double layer at nanoscale through theoretical and experimental analysis. Under the premise of the constant solvation sheath structure of Li+ in bulk electrolyte, a trace amount of lithium nitrate (LiNO3) and copper fluoride (CuF2) were employed into electrolytes to build robust electric double layer structures on Li metal sur-face. The distinct results were achieved with the initial competitive adsorption of bis(fluorosulfonyl)imide ion (FSI-), fluoride ion (F-) and nitrate ion (NO3-) in inner Helmholtz plane. As a result, Cu-NO3- complexes are preferentially adsorbed and reduced to form SEI. The modified Li metal electrode can achieve an average Coulombic efficiency of 99.5% over 500 cycles, enabling a long lifespan and high capacity retention of practical rechargeable batteries. The mechanism as-proposed bridges the gap between Li+ solvation and the adsorption about the electrode interface formation in a working battery.

We report the first total synthesis of (+)-granatumine A, a limonoid alkaloid with PTP1B inhibitory activity, in ten steps. Over the course of this study, two key methodological advances were made: a cost-effective procedure for ketone α,β-dehydrogenation using allyl-Pd catalysis, and a Pd-catalyzed protocol to convert epoxyketones to 1,3-diketones. The central tetrasubstituted pyridine is formed by a convergent Knoevenagel condensation and carbonyl-selective electrocyclization cascade, which was followed by a direct transformation of a 2H-pyran to a pyridine. These studies have led to the structural revision of two members of this family.

Cyclic imines, generated in situ from their corresponding N-lithiated amines and a ketone hydride acceptor, undergo reactions with a range of organometallic nucleophiles to generate α-functionalized amines in a single operation. Activation of the transient imines by Lewis acids that are compatible with the presence of lithium alkoxides was found to be crucial to accommodate a broad range of nucleophiles including lithium acetylides, Grignard reagents, and aryllithiums with attenuated reactivities.

Soft porous crystals (SPCs) that exhibit stimuli-responsive dynamic sorption behavior are attracting interest for gas stor-age/separation applications. However, design and synthesis of SPCs is challenging. Herein, we report a new type of SPC based on a [2+3] imide-based organic cage (NKPOC-1) and find that it exhibits guest-induced breathing behavior. Various gases were found to induce activated NKPOC-1 crystals to reversibly switch from a "closed" nonporous phase (α) to two porous "open" phases (β and γ). The net effect is gate-opening behavior induced by CO2 and C3 hydrocarbons. Interestingly, NKPOC-1-α selectively adsorbs propyne over propylene and propane at ambient conditions. Thus, NKPOC-1-α has the potential to separate binary and ternary C3 hydrocarbon mixtures and performance was subsequently verified by fixed bed column breakthrough experiments. In addition, molecular dynamics calculations and in situ X-ray diffraction experiments indicate that the gate-opening effect is accompanied by reversible structural transformations. The adsorption energies from molecular dynamics simulations aid are consistent with the experimentally observed selective adsorption phenomena. The understanding gained from this study of NKPOC-1 supports the further development of SPCs for applications in gas separa-tion/storage since SPCs do not inherently suffer from the recyclability problems often encountered with rigid materials.

Direct conversion of dinitrogen (N2) into organic compounds, not through ammonia (NH3), is of great significance both fundamentally and practically. Here, we report a scandium-mediated high-efficient synthetic cycle affording hydrazine derivatives (RMeN-NMeR') directly from N2 molecule and carbon-based electrophiles. The cycle includes three main steps: i) reduction of halogen-bridged discandium complex under N2 leading to (N2)3--bridged discandium complex via (N2)2- intermediate, ii) treatment of the (N2)3- complex with methyl triflate (MeOTf) affording (N2Me2)2--bridged discandium complex, and iii) further reaction of the (N2Me2)2- complex with carbon-based electrophiles producing hydrazine derivatives along with regeneration of the halide precursor. Furthermore, insertion of a CO molecule into one Sc-N bond in the (N2Me2)2--scandium complex was observed. Most notably, this is the first example of rare-earth metal-promoted direct conversion of N2 to organic compounds; the formation of C-N bonds by the reaction of these (N2)3- and (N2Me2)2- complexes with electrophiles represents the first case among all N2-metal complexes reported.

Cyclic peptides have provided one of the most important platforms for exploration of biorelevant chemical space between small molecules and biologics. However, in comparison with the design and synthesis of small molecules, chemists' ability to fine tune the three-dimensional structures and properties of cyclic peptides lag far behind. Intrigued by cyclophane peptide natural products, we wondered whether the rigid, planar and hydrophobic cyclophane motif could provide a new design element for the synthesis of cyclic peptides with well-behaved 3D structures. Herein, we report a generally applicable method for synthesis of natural-product-like cyclophane-braced peptide macrocycles via Pd-catalyzed intramolecular C(sp3)-H arylation with aryl iodides at the remote γ position of various N-terminal aliphatic amino acid units using a simple picolinamide directing group. Products of high structural and stereochemical complexity were quickly assembled from easily accessible peptide precursors prepared by standard solid phase peptide synthesis. Many of these peptide macrocycles show highly ordered structures as revealed by X-ray crystallography. Remarkably, the PA-directed C(sp3)-H cyclization reac-tion of unprotected peptide substrates carrying various free polar side chains proceeded with high efficiency and selectivity in aqueous media. This demonstrates not only the synthetic utility of Pd-catalyzed C(sp3)-H functionalization reactions, but also offers a valuable new orthogonal reactivity for peptide chemistry.

A series of thorium(IV)-imido complexes was synthesized and characterized. Extensive experimental and computational comparisons with the isostructural cerium(IV)-imido complexes revealed a notably more covalent bonding arrangement for the Ce=N bond compared with the more ionic Th=N bond. The thorium-imido moieties were observed to be three orders of magnitude more basic than their cerium congeners. More generally, these results provide unique experimental evidence for the larger covalent character of 4f05d0 Ce(IV) multiple bonds compared to its 5f06d0 Th(IV) actinide congener.

We report here a catalytic method for the modular ring expansion of cyclic aliphatic alcohols. In this work, proton-coupled electron transfer (PCET) activation of an allylic alcohol sub-strate affords an alkoxy radical intermediate that undergoes subsequent C-C bond cleavage to furnish an enone and a tethered alkyl radical. Recombination of this alkyl radical with the revealed olefin acceptor in turn produces a ring-expanded ketone product. The regioselectivity of this C-C bond-forming event can be reliably controlled via substituents on the olefin substrate, providing a means to convert a simple N-membered ring substrate to either N+1 or N+2 ring adducts in a selective fashion.

NMR based crystallography approaches involving the combination of crystal structure prediction methods, ab-initio calculated chemical shifts and solid-state NMR experiments are a powerful approach for crystal structure determination of microcrystalline powders. However, currently structural information obtained from solid state NMR is usually included only after a set of candidate crystal structures has already been independently generated, starting from a set of single molecule conformations. Here, we show with the case of ampicillin that this can lead to failure of structure determination. We propose a crystal structure determination method that includes experimental constraints during conformer selection. In order to overcome the problem that experimental measurements on the crystalline samples are not obviously translatable to restrict the single molecule conformational space, we propose constraints based on the analysis of absent cross-peaks in solid-state NMR correlation experiments. We show that these absences provide unambiguous structural constraints on both the crystal structure and the gas phase conformations, and therefore can be used for unambiguous selection. The approach is parameterized on the crystal structure determination of flutamide, flufenamic acid, and cocaine, where we reduce the computational cost by around 50%. Most importantly, the method is then shown to correctly determine the crystal structure of ampicillin, which would have failed using current methods because it adopts a high energy conformer in its crystal structure. The average positional RMSE on the NMR powder structure is 〈r_av 〉=0.176 Å, which corresponds to an average equivalent displacement parameter U_eq=0.0103 Å^2.

Photocycloadditions are often typified by the oxetane forming Paternò-Büchi reaction. However, the mechanistic constraints of carbonyl excitation and olefin interception have limited this attractive oxetane forming pathway. Here we describe the use of a Cu(I) pre-catalyst that achieves selective olefin activation via coordination to the metal center. Significantly, this intermolecular 2+2 carbonyl-olefin photocycloaddition engages alkyl ketones which are more challenging to accommodate via direct irradiation pathways. Mechanistic investigations support the in situ formation of a Cu-norbornene resting state that undergoes a MLCT leading to oxetane formation.

Hydrogen-bonded organic framework (HOF)-based catalysts still remain unreported thus far due to their relatively weak stability. In the present work, a robust porous HOF (HOF-19) with a Brunauer-Emmett-Teller surface area of 685 m2 g‒1 was reticu-lated from a cage-like building block, amino-substituted bis(tetraoxacalix[2]arene[2]triazine), depending on the hydro-gen bonding with the help of - interactions. The post-synthetic metalation of HOF-19 with palladium acetate afforded a palladium(II)-containing heterogeneous catalyst with hydro-gen-bonded structure retained, which exhibits excellent catalyt-ic performance for Suzuki-Miyaura coupling reaction with the high isolation yields (96~98%), prominent stability, and good selectivity. More importantly, by simple recrystallization, the catalytic activity of deactivated species can be recovered from the isolation yield 46% to 92% for 4-bromobenzonitrile conver-sion at the same conditions, revealing the great application potentials of HOF-based catalysts.

The structural and functional diversity of proteins combined with their genetic programmability has made them indispensable modern materials. Well-defined, hollow protein capsules have proven to be particularly useful due their ability to compartmentalize macromole-cules and chemical processes. To this end, viral capsids are common scaffolds and have been successfully repurposed to produce a suite of practical protein-based nanotechnologies. Recently, the recapitula-tion of viromimetic function in protein cages of nonviral origin has emerged as a strategy to both complement physical studies of natural viruses and produce useful scaffolds for applications. In this perspec-tive, we review recent progress toward generation of virus-like behav-ior in nonviral protein cages through rational engineering and di-rected evolution. These artificial systems can aid our understanding of the emergence of viruses from existing cellular components, as well as provide alternative approaches to tackle problems and open up new opportunities in medicine and biotechnology.

Backbone N-methylations impart several favorable characteristics to peptides including increased proteolytic stability and membrane permeability. Nonetheless, amide bond N-methylations incorporated as post-translational modifications are scarce in nature, and were first demonstrated in 2017 for a single set of fungal metabolites. Here we expand on our previous discovery of iterative, autocatalytic α- N-methylating precursor proteins in the borosin family of ribosomally encoded peptide natural products. We identify over fifty putative pathways in a variety of ascomycete and basidiomycete fungi, and functionally validate nearly a dozen new self-α- N-methylating catalysts. Significant differences in precursor size, architecture, and core peptide properties subdivide this new peptide family into three discrete structural types. Lastly, using targeted genomics, we link the biosynthetic origins of the potent antineoplastic gymnopeptides to the borosin natural product family. This work highlights the metabolic potential of fungi for ribosomally synthesized peptide natural products.

Template assistance allows organic reactions to occur under highly diluted conditions - where intermolecular reactions often fail to proceed - by bringing reactants into close spatial proximity. This strategy has been elegantly applied to numerous systems, but always with the retention of at least one of the templating groups in the product. In this report, we describe a traceless, templated amide-forming ligation that proceeds at low micromolar concentration under aqueous conditions in the presence of biomolecules. We utilized the unique features of an acylboronate-hydroxylamine ligation, in which covalent bonds are broken in each of the reactants as the new amide bond is formed. By using streptavidin as a template and acylboronates and O-acylhydroxylamines bearing desthiobiotins that are cleaved upon amide formation, we demonstrate that traceless, templated ligation occurs rapidly even at sub-micromolar concentrations. The requirement for a close spatial orientation of the functional groups - achieved upon binding to streptavidin - is critical for the observed enhancement in the rate and quantity of product formed.

Hydrogen-atom transfer (HAT) from a substrate carbon to an iron(IV)-oxo (ferryl) intermediate initiates a diverse array of enzymatic transformations. For outcomes other than hydroxylation, coupling of the resultant carbon radical and hydroxo ligand (oxygen rebound) must generally be averted. A recent study of FtmOx1, a fungal iron(II)- and 2-(oxo)glutarate-dependent oxygenase that installs the endoperoxide of verruculogen by adding O2 between carbons 21 and 27 of fumitremorgin B, posited that tyrosine (Tyr or Y) 224 serves as HAT intermediary to separate the C21 radical (C21•) and Fe(III)-OH HAT products and prevent rebound. Our re-investigation of the FtmOx1 mechanism revealed, instead, direct HAT from C21 to the ferryl complex and surprisingly competitive rebound. The C21-hydroxylated (rebound) product, which undergoes deprenylation, predominates when low [O2] slows C21•-O2 coupling in the next step of the endoperoxidation pathway. This pathway culminates with addition of the C21-O-O• peroxyl adduct to olefinic C27 followed by HAT to the C26• from a Tyr. The last step results in sequential accumulation of Tyr radicals, which are suppressed without detriment to turnover by inclusion of the reductant, ascorbate. Replacement of each of four candidates for the proximal C26 H• donor (including Y224) with phenylalanine (F) revealed that only the Y68F variant (i) fails to accumulate the first Tyr• and (ii) makes an altered major product, identifying Y68 as the donor. The implied proximities of C21 to the iron cofactor and C26 to Y68 support a new structural model of the enzyme-substrate complex that is consistent with all available data.